1. Field of the Invention
This invention relates in general to methods and apparatus for collecting and testing a viscous liquid or gel. Apparatus and methods are disclosed for collecting and pooling the contents of a plurality of relatively small containers. The invention is especially useful for microbiological testing a product sample with respect to sterility, bacteriostasis, or preservative effectiveness.
2. Description of the Related Art
In the production of consumer products in the health care or pharmaceutical industries, in which liquids of various viscosities are sold in relatively small containers for individual use, microbiological testing on a statistical basis may be required to ensure that the products are substantially free of microorganisms such as bacteria, fungi and molds. Recognized procedures for such microbiological testing may involve the direct transfer method or the membrane filter method. These methods are described in the United States Pharmacopeia (USP) 23 (1994), U.S. Food and Drug Administration Guidelines (FDA), and the Japanese Pharmacopeia XII suppl. II, all incorporated herein by reference.
One conventional method of microbiological testing is the antimicrobial preservative-effectiveness procedure (or "preservative efficacy" procedure), normally a direct transfer method. In the direct transfer method, microorganisms are inoculated directly into a sample solution, provided that the sample size of that solution is of sufficiently ample size (normally at least 20 mL). The solutions are then plated out in conventional media and subsequently examined at periodic intervals of 7, 14, 21 and 28 days. When the amount of sample obtained from a single product container is too small to allow the sample to be directly inoculated, a plurality of containers from a sample lot may be pooled together (under sterile conditions to avoid contamination) and then the pooled contents directly inoculated.
Another standard microbiological test, sterility testing, typically involves the membrane filter method. In the membrane filter method, a test sample is filtered through a membrane filter. Typically, the filter is then rinsed to remove any microbiocides, after which the filter holding the retentate from the test sample, or a preselected fraction of this filter, is incubated in a suitable medium. Optionally, the medium may be added onto the membrane filter while remaining in the filtration device.
In the health care industry, in order to obtain an adequate amount of test solution for sterility testing a product, twenty bottles or more per sample lot may need to be pooled or combined. In order to obtain an adequate amount of test solution for the previously mentioned preservative efficacy test, as many as eighty containers or bottles per sample lot may need to be combined. The pooling of such large numbers of bottles can be very time consuming and difficult when the sample containers are small, the contents are relatively viscous, and/or the bottle is designed to expel the liquid contents dropwise. If the containers have a separate top piece or dispenser tip that is removable from the container, then the tip can be removed, the bottle inverted, and the solution dispensed relatively easily, especially when the solution is non-viscous. Typically, however, the dispensing tip snuggly fits into the neck portion of a bottle, and removal of such container tips can be time consuming and laborious.
It may be particularly problematic or difficult to transfer a viscous solution from a single-piece container having a dispensing tip that is an irremovable or integral part of the container holding the solution. Such containers include form-filled bottles or tubes, either unit-dose or multi-dose containers. A conventional method of collecting a sample from a container having an irremovable tip involves repetitively squeezing the outside surface of the container to force its contents out its dispensing orifice as quickly as possible. To dispense the entire contents of the necessary number of bottles by such a method may be a strenuous and monotonous task, particularly when the bottles are semi-rigid and designed to deliver droplets. Also, such a method may result in sample contamination as a result of air being drawn back into a container.
There are many devices available for sterility testing of liquids. For instance, U.S. Pat. No. 4,036,698 relates in general to the testing of pharmacological products. The patent describes and claims an apparatus designed to carry out a membrane filtration method wherein the solution to be tested is added to a filter apparatus comprising a cylindrical canister having two ports at one end and a single port at the opposite end. One of the two ports at the one end is provided with a hydrophobic microporous filter that allows the flow of air therethrough in either direction while screening out any microorganisms. A second membrane filter is positioned within the cylinder such that test solution passes therethrough, trapping bacteria or fungi on the membrane filter. This apparatus does not solve or address the above-mentioned difficulties of collecting a sufficient amount of sample contents from many relatively small containers, particularly containers designed for the delivery of droplets.
In view of the above, there is a need for a more efficient method and apparatus for collecting samples for the microbiological testing of products produced in the pharmaceutical or health care industries. There is a need for a more efficient method of collecting samples from product containers designed to deliver droplets during individual use.